Development of sustained release formulation by using crystal transition of active ingredient.

• Project/Area Number: 26460039
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: Itai Shigeru 静岡県立大学, 薬学部, 教授 (80453059)
• Co-Investigator(Kenkyū-buntansha): 岩尾 康範 静岡県立大学, 薬学部, 准教授 (30433022) ; 野口 修治 東邦大学, 薬学部, 教授 (60237823)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: sustained release / gastro-floating / Clarithromycin / polymorphism / クラリスロマイシン / 結晶転移 / 胃内滞留製剤 / 製造コスト削減 / 胃内浮遊性製剤 / ヘリコバクタピロリ除菌 / 溶融造粒 / 高薬物含有微粒子 / 放射光X線CT / 放出制御製剤

Outline of Final Research Achievements

Clarithromycin(CAM) has 2 crystal forms at ambient temperature and meta-stable crystal(FormⅠ) transforms to stable crystal(FormⅡ) and hydrate(FormⅣ) immediately by contact with water. By using this property, we succeeded in development of highly --loaded CAM sustained release formulation with 0-order manner and gastro-floating formulation. FormⅡ can be obtained by dispersion in water-filtration-drying processes or heat treatment(150℃). Since these treatment lead to increase API cost, we tried and establish the transformation of FormⅠto FromⅡ during the manufacturing process of CAM formulation.

Research Products

• [Journal Article] Effect of gel formation on the dissolution behavior of clarithromycin tablets. (2017)
  • Author(s): Inukai K, Takiyama K, Noguchi S, Iwao Y, Itai S
  • Journal Title: International Journal of Pharmaceutics Volume: 521 Issue: 1-2 Pages: 33-39
  • DOI: 10.1016/j.ijpharm.2017.01.065
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes (2017)
  • Author(s): Ali MA, Kataoka N, Ranneh AH, Iwao Y, Noguchi S, Oka T, Itai S.
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 65 Issue: 1 Pages: 42-48
  • DOI: 10.1248/cpb.c16-00513
  • NAID: 130005187634
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Saturated fatty acids and fatty acid esters promote the polymorphic transition of clarithromycin metastable form I crystal. (2016)
  • Author(s): Watanabe M, Mizoguchi M, Aoki H, Iwao Y, Noguchi S, Itai S.
  • Journal Title: International Journal of Pharmaceutics Volume: 512 Issue: 1 Pages: 108-117
  • DOI: 10.1016/j.ijpharm.2016.08.041
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process. (2016)
  • Author(s): Terada T, Tagami M, Ohtsubo T, Iwao Y, Noguchi S, Itai S.
  • Journal Title: International Journal of Pharmaceutics Volume: 509 Issue: 1-2 Pages: 328-337
  • DOI: 10.1016/j.ijpharm.2016.05.061
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing α-Monoglyceride Additives (2016)
  • Author(s): Ali MA, Noguchi S, Iwao Y, Oka T, Itai S
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 64 Issue: 6 Pages: 577-584
  • DOI: 10.1248/cpb.c15-00984
  • NAID: 130005154404
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication (2015)
  • Author(s): Aoki, H., Iwao, Y., Mizoguchi, M., Noguchi, S., Itai, S
  • Journal Title: European Journal of Pharmaceutics and Biopharmaceutics Volume: 92 Pages: 22-27
  • DOI: 10.1016/j.ejpb.2015.02.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Suppressed release of clarithromycin from tablets by crystalline phase transition of metastable polymorph form I (2015)
  • Author(s): Fujiki, S., Watanabe, N., Iwao, Y., Noguchi, S., Mizoguchi, M., Iwamura, T., Itai, S.
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 104 Issue: 8 Pages: 2541-2644
  • DOI: 10.1002/jps.24516
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effect of surfactants or a water soluble polymer on the crystal transition of clarithromycin during a wet granulation process (2015)
  • Author(s): Nozawa, K., Iwao, Y., Noguchi, S., Itai, S
  • Journal Title: International Journal of Pharmaceutics Volume: 495 Issue: 1 Pages: 204-217
  • DOI: 10.1016/j.ijpharm.2015.08.080
  • Peer Reviewed
• [Journal Article] Polymorphic transformation of antibiotic clarithromycin under acidic condition (2014)
  • Author(s): Noguchi, S., Takiyama, K., Fujiki, S., Iwao, Y., Miura, K., Itai, S.
  • Journal Title: Journal of Pharmaceutical Sciences, Volume: 103 Pages: 580-586
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluation of the physicochemical properties of fine globular granules prepared by a multi-functional rotor processor (2014)
  • Author(s): Kimura, S., Iwao, Y., Ishida, M., Noguchi, S., Itai, S., Uchida, S., Yamada, M., Namiki, N.
  • Journal Title: Chemical & Pharmaceutical Bulletin Volume: 62 Pages: 1-7
  • NAID: 130003390776
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of the centrifugal coating and centrifugal fluidized bed coating methods on the physicochemical properties of sustained-release microparticles using a multi-functional rotor processor (2014)
  • Author(s): Yamada, N., Mise, R., Ishida, M., Iwao, Y., Noguchi, S., Itai, S.
  • Journal Title: Advanced Powder Technology Volume: 25 Pages: 430-435
  • Peer Reviewed
• [Journal Article] Development and evaluation of a tacrolimus cream formulation using a binary solvent system (2014)
  • Author(s): Yamanaka, M., Yokota, S., Iwao, Y., Noguchi S., Itai, S.
  • Journal Title: International Journal of Pharmaceutics Volume: 464 Pages: 19-26
  • Peer Reviewed
• [Journal Article] Development of highly stable nifedipine solid-lipid nanoparticles (2014)
  • Author(s): Barman, RK., Iwao, Y., Funakoshi, Y., Ranneh, AH., Noguchi S., Wahed, MII., Itai, S.
  • Journal Title: Chemical & Pharmaceutical Bulletin Volume: 62 Pages: 1-8
  • NAID: 130004053796
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In vivo pharmacokinetic and hemocompatible evaluation of lyophilization induced nifedipine solid-lipid nanoparticle (2014)
  • Author(s): Barman, RK., Iwao, Y., Islam, Md., Funakoshi, Y., Noguchi S., Wahed, MII., Itai, S
  • Journal Title: Pharmacology & Pharmacy Volume: 5 Pages: 455-461
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Impact of active ingredients on the swelling properties of orally disintegrating tablets prepared by microwave treatment (2014)
  • Author(s): Sano, S., Iwao, Y., Noguchi S., Kimura, S., Itai, S.
  • Journal Title: International Journal of Pharmaceutics Volume: 468 Pages: 234-242
  • Peer Reviewed
• [Presentation] 親水性高分子を用いたクラリスロマイシン準安定形結晶含有造粒物の調製 (2017)
  • Author(s): 渡邉美笛、岩尾康範、野口修治、木村晋一郎、板井茂
  • Organizer: 日本薬剤学会第32年会
  • Place of Presentation: 大宮
  • Year and Date: 2017-05-13
• [Presentation] cryo-TEM及びAFMによる脂質ナノ粒子の構造解析 (2017)
  • Author(s): 松尾聖羅、岩尾康範、東顕二郎、森部久仁一、木村晋一郎、板井茂
  • Organizer: 日本薬剤学会第32年会
  • Place of Presentation: 大宮
  • Year and Date: 2017-05-11
• [Presentation] 飽和脂肪酸や脂肪酸エステルが薬物の結晶転移に与える影響 (2016)
  • Author(s): 渡邉美笛、岩尾康範、野口修治、板井茂
  • Organizer: 日本病院薬剤師会東海ブロック・日本薬学会東海支部会 合同学術大会
  • Place of Presentation: 岐阜
  • Year and Date: 2016-10-30
• [Presentation] クラリスロマイシンのゲル化による溶出挙動への影響とゲル形成機構に関する研究 (2016)
  • Author(s): 犬飼晃基、瀧山圭、岩尾康範、野口修治、板井茂
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 岐阜
  • Year and Date: 2016-05-19
• [Presentation] Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing α-Monoglyceride Additives (2016)
  • Author(s): アリ モハマド アシュラフ、岩尾康範、野口修治、岡俊彦、板井茂
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 岐阜
  • Year and Date: 2016-05-19
• [Presentation] クラリスロマイシン/脂質mixtureにおけるクラリスロマイシン結晶転移メカニズムの解明 (2016)
  • Author(s): 渡邉美笛
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜」
  • Year and Date: 2016-03-28
• [Presentation] カルボン酸塩によるクラリスロマイシンの放出抑制効果 (2015)
  • Author(s): 板井茂
  • Organizer: 日本薬剤学会第30年会
  • Place of Presentation: 長崎
  • Year and Date: 2015-05-21
• [Presentation] クラリスロマイシンの除菌効果増強を目的とした薬物高含有胃内浮遊性粒子の設計と評価 (2014)
  • Author(s): 溝口緑理、青木肇、岩尾康範、野口修治、板井茂
  • Organizer: 日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会
  • Place of Presentation: 静岡
  • Year and Date: 2014-11-09
• [Presentation] Preparation and Evaluation of Gastro-Floating Fine Granules Prepared by Melt Granulation and Highly Loaded with Clarithromycin for Helicobacter Pylori Eradication (2014)
  • Author(s): Hajime Aoki, Midori Mizoguchi, Yasunori Iwao, Shuji Noguchi, and Shigeru Itai.
  • Organizer: 2014 American Association of Pharmaceutical Scientists Annual Meeting and Exposition
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-11-05
• [Presentation] 撹拌溶融造粒法を用いたいクラリスロマイシン高含有胃内浮遊性微小粒子の設計と評価 (2014)
  • Author(s): 青木肇、溝口緑理、岩尾康範、野口修治、板井茂
  • Organizer: 製剤機械技術学会第24回大会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-10-08
• [Presentation] ヘリコバクター・ピロリ除菌を目的としたクラリスロマイシン高含有胃内浮遊性粒子の設計と評価 (2014)
  • Author(s): 青木肇、溝口緑理、岩尾康範、野口修治、板井茂
  • Organizer: 第 60 回 日本薬学会東海支部 総会・大会
  • Place of Presentation: 鈴鹿
  • Year and Date: 2014-07-05
• [Presentation] 放射光X線CT法を用いたワックスマトリックス製剤の溶出機構の解析 (2014)
  • Author(s): 岩本翔、野口修治、岩尾康範、板井茂
  • Organizer: 日本薬剤学会第29年会
  • Place of Presentation: 大宮
  • Year and Date: 2014-05-20
• [Presentation] 放射光X線CT法を用いた錠剤内部構造解析 (2014)
  • Author(s): 梶原隆介、野口修治、岩尾康範、鈴木芳夫、寺田靖子、上杉健太朗、板井茂
  • Organizer: 日本薬剤学会第29年会
  • Place of Presentation: 大宮
  • Year and Date: 2014-05-20
• [Presentation] 撹拌溶融造粒法によるクラリスロマイシン高含有胃内浮遊性粒子の設計と評価 (2014)
  • Author(s): 青木肇、岩尾康範、野口修治、板井茂
  • Organizer: 日本薬剤学会第29年会
  • Place of Presentation: 大宮
  • Year and Date: 2014-05-20
• [Remarks] 静岡県立大学薬学部 創剤科学分野 創剤工学研究室
  • URL: http://w3pharm.u-shizuoka-ken.ac.jp/pharmeng/